By Mandy Roth
Now you see tremors; now you don't.
An incisionless surgical treatment that delivers focused ultrasound waves to destroy targeted brain tissue often results in immediate symptom reduction or relief for patients with tremor-predominant Parkinson's disease. The procedure, which combines focused ultrasound technology with magnetic resonance imaging (MRI), recently received FDA approval and provides an option for patients who cannot take or do not respond to medication. It also offers an alternative to deep brain stimulation (DBS), a more invasive form of treatment, which implants hardware into the patient's body.
Exablate Neuro technology is available at Penn Medicine in Philadelphia and is already used by 13 U.S. medical centers for treatment of a separate condition, essential tremor, which has similar characteristics and often demonstrates the same instantaneous results. The FDA approved the technology for treatment of essential tremor in 2016.
Nearly 2,000 patients have been treated for one of these two conditions in one of 50 medical facilities globally, and the waiting list at Penn Medicine is growing. More healthcare systems will soon offer the treatment for tremor-resistant Parkinson's, although financial reimbursement through government or private payers is not yet available.
In addition to treating movement disorders, INSIGHTEC, the company that developed this technology, is working with leading research institutions on clinical studies for numerous other purposes, including treatment of Alzheimer's, epilepsy, and brain tumors, as well as its possible ability to temporarily disrupt the blood-brain barrier to allow targeted drug delivery. Clinical trials are underway for all of these applications.
"We're still in the early stages of this technology, and I think there's going to be a lot of development in terms of what can be done with it," says neurosurgeon Gordon H. Baltuch, MD, PhD, professor of neurosurgery at the University of Pennsylvania Perelman School of Medicine. Baltuch practices at Pennsylvania Hospital in Philadelphia, one of six hospitals in the Penn Medicine system, and uses the innovation to treat patients with tremor-predominant Parkinson's, as well as essential tremor.
Baltuch and Maurice Ferré, MD, CEO and chairman of board of INSIGHTEC, provide a look into how this treatment works and the potential that exists for this novel form of technology.
How the Innovation Works
One advantage of ultrasound is that it does not damage the tissue it passes through, yet focusing multiple waves on a targeted area produces heat, which can destroy, or ablate, the tiny area of the brain causing the tremors.
Finding a way to get ultrasound to penetrate the dense tissue of the skull and accommodate individual variability took years of development. INSIGHTEC, which was founded in 1999 and has dual headquarters in Haifa, Israel, and Miami, developed hardware that produced ultrasound powerful enough to penetrate the skull, and software that corrects for skull shape and thickness.
The technology often can use a facility's existing MRI, Ferré says, which enables the neurosurgeon to guide the high-energy focused ultrasound waves. The procedure is known as MRgFUS and the treatment is an incisionless thalamotomy.
Patients are awake during the process and wear a special helmet that delivers the ultrasound treatment from inside the MRI machine. They typically start the session unable to drink water from a glass or write legibly because of tremors. Before the ablation occurs, the medical team does preliminary testing to ensure the proper brain location is pinpointed.
Treatment Delivers Immediate Results
When the process is complete, tremors on the treated side of the body often completely disappear.
An online video demonstrates Baltuch performing the procedure on a patient with essential tremor. Before treatment the patient tries to bring a cup of water to his mouth, but his tremors prevent him from doing do. After the procedure, he is shown touching the tips of his two index fingers together, remarking, "I couldn't do this an hour or so ago." He later brings a water cup directly to his lips with no tremor.
"This has really been my second epiphany in medicine," says Baltuch. "My first in this field was when we saw the early deep brain stimulation videos." Watching patients' symptoms instantly disappear "was like magic," he says. Witnessing patients discover their Parkinson's tremors have vanished following a procedure, "is the same thing. When you see it, it's phenomenal."
Limitations, Side Effects, and Long-Term Outlook
Baltuch cautions, however, that focused ultrasound thalamotomy is not without risk or side effects, there are limitations, and there are not yet long-term studies.
•Side effects: Side effects include difficulty walking or unsteadiness following the procedure, along with tingling or numbness in the lips or fingers. Most issues resolve within months.
•Limitations: Currently, only one side of the body can be treated. Earlier forms of surgical ablation sometimes resulted in speech difficulties, so for now, the FDA has limited treatment to one side of the brain. The side that controls the patient's dominant hand is usually targeted. INSIGHTEC is exploring bilateral treatment in medical centers outside the U.S. In addition, while treatment can reduce or eliminate tremors on one side of the body, it does not stop other symptoms of Parkinson's or slow disease progression.
•Long-term studies: Because five- and 10-year studies have not yet been conducted, "We don’t yet [know the] long-term effectiveness" of focused ultrasound thalamotomy for tremor-dominant Parkinson's and essential tremor, says Baltuch. "The published data show that this may not be as effective in tremor reduction as, potentially, deep brain stimulation can. And, although it's non-invasive, you're still making a thermal lesion [on the brain]."
DBS or Focused Ultrasound?
DBS also has risks, Baltuch says. The procedure involves implanting one or more electrodes in the brain, a neurostimulator in the neck, and a wire connecting the two devices.
"You're drilling a hole [in the brain] and you're putting hardware [in the brain and body]," he says. "It's neurosurgery and, yes, it carries a risk of hemorrhaging, stroke, and infection. But the simulator itself is not making a lesion; you're neuro-modulating the brain in some way to … get rid of the tremor. You can potentially dial it up or dial it down. With a thalamotomy, there really is no eraser."
Medication is still the first line of defense for treatment of tremors for patients with either of these conditions. For patients who are medication refractory, Baltuch says there are pros and cons to both procedures.
Focused ultrasound guided thalamotomy "is a great technology to have in addition to a deep brain stimulation," says Baltuch. "I see it more at the moment as it as complimentary. I present the pluses and minuses of each technique to patients and their families, I'll give them my recommendation, and then I'll let them make a choice."
Ferré points to data that he says demonstrates the enormity of the problem and the potential for another treatment option.
"There are approximately 10 million Americans living with essential tremor," he says. "Up to 50% of these patients are refractory to medication." Altogether, essential tremor patients cost the U.S. healthcare system about $142 billion annually, according to a report commissioned by consulting firm Frost & Sullivan. In addition, Ferré adds, "Nearly one million people will be living with Parkinson's disease in the U.S. by 2020, and in an estimated 26% of these patients, the primary symptom is tremor. Only a small percentage seek DBS intervention."
"We think the majority of these patients have opted not to be treated because they don't want the invasiveness of being treated with a deep brain stimulator or with this hardware," Ferré says.
According to a study published in Movement Disorders on July 25, 2015, 24,000 estimated DBS surgeries were performed in the United States for Parkinson's and essential tremor between 1998 and 2007, with Parkinson's patients undergoing most of the surgeries.
Technology Holds Potential to Change Surgical Trends
Meanwhile, INSIGHTEC is exploring a much bigger canvas. The company has identified over a hundred different diseases that it could target with its Exablate Neuro technology, says Ferré.
"The trend is to try to treat diseases earlier in their cycle," he says, adding that focused ultrasound treatment may become a tool in this regard. In addition, "This technology, as a platform, has the capabilities of transforming the way we look at surgery. If you look at the trends of surgeries, you've seen it go from open surgery, to laparoscopic surgery, to robotic surgery. We think we're now the next generation—incisionless surgery— which is completely noninvasive."